Two strains of obese mouse (ob/ob and NZO) respond to treatment with the hormone, pancreatic polypeptide (PP) by reduction in rate of weight gain and decreased hyperphagia (ob/ob). A hypothesis has been put forward that these mice have a genetic deficiency of PP. It is proposed to test this hypothesis by developing a specific radioimmunoassay for murine PP and applying it to study variations in pancreatic islet cell populations and pancreatic PP content as a function of age, and therefore, stage of the obese syndrome in obese mice. Plasma PP levels will be studied as a function of season, time of day and mouse age. Factors which stimulate PP secretion will be compared in normal and obese mice by measuring plasma PP before and after feeding and after stimulation with cholinergic agonists and antagonists. Further studies of PP secretion will be performed by islet cell perfusion. An attempt will be made to characterize (molecular size) the PP produced and secreted in obese mice.